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Background Wheezing, starting early in life, is a heterogeneous medical condition caused by airway obstruction due to different underlying mechanisms. Primary immunodeficiencies are also among the risk factors that cause wheezing and recurrent bronchiolitis. ADA deficiency is a primary immunodeficiency, also a rare metabolic disease associated with multisystemic clinical findings. Objective This report will be helpful for adressing the importance of thinking primary immunodeficiency in case of wheezing and recurret bronchiolitis. Methods The patient was diagnosed by using a targeted next generation sequencing PID panel. Lymphocyte subsets were measured by flow-cytometry. Results Here we present an infant with ADA deficiency who admitted with wheezing and recurrent bronchiolitis as the first presentation. He was found to have wheezing, relative CD4+ T cell deficiency, and prolonged neutropenia. Conclusion Primary immunodeficiencies including ADA deficiency should be considered in infants with wheezing, recurrent bronchiolitis, lymphopenia and neutropenia.

Background Pulmonary involvement which can be infectious or noninfectious is one of the most frequent complications in patients with primary immunodeficiency (PID). Objective The aim of this study is to assess the pulmonary system of the pediatric patients with PID and report the demographical, clinical, and radiological findings regarding the underlying PID. Methods The present study included pediatric patients who were receiving immunoglobulin replacement therapy (IGRT) for PID (combined immunodeficiency [CVID] (23), common variable immunodeficiency (15), and agamaglobulinemia [10]) so far or newly diagnosed and started IGRT at Hacettepe University Immunology Department, between January 2015 and January 2018. Results A total of 48 patients (60.4% male), aged 9.9 (6.1-14) years were included. Time of delay in the diagnosis of immundeficiency was 2.27 (interquartile range: 1.0-6.75) years. CVID patients exhibited higher respiratory system symptoms, as well as a history of recurrent lung infection and hospitalization. Hilar and mediastinal lymphadenopathies, peribronchial thickening, and bronchiectasis were the most common pulmonary complications and more than three lung lobes were affected in 69%. Among the newly diagnosed patients, bronchiectasis was present in 25% and more than three lobes were affected in 62.5%. Although pulmonary nodules and mediastinal lymphadenopathy were frequently computed tomography findings in our patients, only two patients (4.16%) were diagnosed with interstitial lung disease. Conclusion Although bronchiectasis is predominantly reported as a long-term complication in adult patients with PID, half of our pediatric patient cohort with PID had bronchiectasis, even the newly diagnosed patients. Long-term follow-up is needed to assess the extent to which these pulmonary complications that develop in the natural course of the disease can be prevented by IGRT.

Background: Chronic granulomatous disease (CGD), one of the phagocytic system defects, is the primary immunodeficiency caused by dysfunction of the NADPH oxidase complex which generates reactive oxygen species (ROS), which are essential for killing pathogenic microorganisms, especially catalase-positive bacteria and fungi. Objective: The objective of our study was to assess the clinical and laboratory characteristics, treatment modalities, and prognosis of patients with CGD. Methods: We retrospectively reviewed 63 patients with CGD who have been diagnosed, treated, and/or followed-up between 1984 and 2018 in Hacettepe University, Ankara, in Turkey, as a developing country. Results: The number of female and male patients was 26/37. The median age at diagnosis was 3.8 (IQR: 1.0–9.6) years. The rate of consanguinity was 63.5%. The most common physical examination finding was lymphadenopathy (44/63), growth retardation (33/63), and hepatomegaly (27/63). One adult patient had squamous cell carcinoma of the lung. The most common infections were lung infection (53/63), skin abscess (43/63), and lymphadenitis (19/63). Of the 63 patients with CGD, 6 patients had inflammatory bowel disease (IBD). Twelve of the 63 patients died during follow-up. CYBA, NCF1, CYBB, and NCF2 mutations were detected in 35%, 27.5%, 25%, and 12.5% of the patients, respectively. Conclusion: We identified 63 patients with CGD from a single center in Turkey. Unlike other cohort studies in Turkey, due to the high consanguineous marriage rate in our study group, AR form of CGD was more frequent, and gastrointestinal involvement were found at relatively lower rates. The rate of patients who treated with HSCT was lower in our research than in the literature. A majority of the patients in this study received conventional prophylactic therapies, which highlight on the outcome of individuals who have not undergone HSCT.

INTRODUCTION Asthma, a common chronic disease in adolescents is impacted by factors affecting quality of life. This study aimed to determine the psychosocial factors of adolescents with asthma and their parents. METHODS The study included 122 adolescents with asthma, 82 healthy controls, and their parents who completed the Asthma Control Test (ACT), Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Brief Symptom Inventory (BSI). RESULTS The mean age was 14.2 ± 1.9 years. ACT score was high and depression was low in patients with good treatment compliance. As the age of the first asthma symptoms/diagnosis increased, somatization, anxiety, hostility and general psychopathology scores increased, as did the somatization score of parents. Parental anxiety score was not related with adolescent BSI scores in the controls but in the study group when it was higher, the anxiety, depression, somatization, and general psychopathology scores were higher. PAQLQ showed that anxiety, negative self-esteem, somatization, depression, and general psychopathology were higher in patients concerned about asthma. Depression and somatization scores were higher in the parents of patients who perceived that "Treatment does not contribute to asthma control." Somatization scores were higher among parents of patients who noted: "Asthma will not pass in the long-term" and "I cannot control asthma." CONCLUSION Higher scores of asthma patients who were anxious about the disease and families who were despondent about treatment demonstrate that health care providers should spend more time informing patients and caregivers. Increasing patient treatment compliance during early adolescence will lessen the psychological burden of the disease.

Takayasu arteritis (TAK) has been rarely reported in patients with immunodeficiency. In this review, we present two cases with childhood-onset TAK (c-TAK) and primary immunodeficiency while reviewing similar cases in the literature. We reviewed the data for our two pediatric patients with c-TAK and primary immunodeficiency. We also reviewed the literature for patients with c-TAK and immunodeficiency from the inceptions of the databases up to November 2021. A 14-year-old patient had lipopolysaccharide-sensitive beige-like anchor (LRBA) deficiency, and a 16-year-old had X-linked severe combined immunodeficiency (X-linked SCID). During the follow-up, they developed findings suggestive of vasculitides such as hypertension, elevation in acute phase reactants, weakness, and weight loss. Thoracoabdominal computed tomography angiography revealed findings consistent with vasculitis involving the aorta and its major branches. Patients were diagnosed with c-TAK, and corticosteroids were given to both patients in the treatment. We identified 11 articles describing 17 TAK patients with immunodeficiency in our literature search. Two of the patients with c-TAK were infected with human immunodeficiency virus (HIV), another patient had Wiskott-Aldrich syndrome, and the other had idiopathic CD4 + T lymphocytopenia. Nine adult patients with TAK were infected with HIV, three patients had common variable immunodeficiency disorder (CVID), and the other had STAT1 gain-of-function mutation. Clinicians should consider that immunodeficiencies may be accompanied by vasculitic conditions such as TAK. Hypertension, increased inflammatory markers, and constitutional symptoms may be red flags for the development of TAK.

BACKGROUND Subcutaneous immunotherapy (SCIT) is the allergen-specific curative treatment of allergic rhinitis. Adverse effects, most of which are local, can be observed during the immunotherapy. These adverse effects have been reported more frequently during the pollen season. The purpose of this study was to estimate the rate of local, large local, and systemic reactions during the treatment, to determine the relationship between adverse reactions and the season in which these reactions occur, as well as the risk factors for adverse reactions during the grass pollen-specific SCIT treatment in children. METHODS We retrospectively collected and analyzed the data of 261 children who administered grass pollen SCIT between 2008 and 2018. RESULTS A total of 261 children (177, 67.8% male), who received grass pollen SCIT, with a mean (±SD) age of 12.0 ± 3.0 years at the initiation of SCIT were enrolled to the study. The number of the patients who experienced local and large local reactions was 109 and 30, respectively. In addition, the number of the patients with systemic reactions was 35. After the 12 284 injections, local reactions occurred in 357 (2.9%), and this was followed by systemic reaction as 55 (0.4%) and large local reactions as 40 (0.3%). Frequency of local (P

Background: Food protein-induced allergic proctocolitis (FPIAP) is a non‐immunoglobulin E (IgE) mediated food allergy that typically presents with blood-mixed mucoid stool. Objective: To identify the predictors that affect the tolerance development in infants with FPAIP and laboratory as well as clinical differences between patients with early and with late tolerance. Methods: A total of 185 infants with FPIAP were included. The patients were grouped and analyzed based on laboratory tests and clinical characteristics. Results: The median (interquartile range [IQR]) age of onset of symptoms was 2.0 months (1.0‐3.0 months). Symptoms began in severe cases in patients (n = 23) at a younger median (IQR) age (1.5 months [0.7‐2.0 months]) than the group with nonsevere presentation (median 2.0 months [IQR 1.5‐3.0 months]) (p < 0.001). The frequency of neutropenia (3) (p = 0.045) and eosinophilia (450 mm3) (p = 0.018) was increased in severe cases. Concomitant IgE-related food allergy (odds ratio [OR] 3.595 [95% confidence interval {CI}, 1.096‐11.788], p = 0.035), non‐IgE-mediated multiple food allergy (OR 3.577 [95% CI, 1.595‐8.018], p = 0.002), feeding with cow's milk‐based formula (at least once during infancy) (OR 2.517 [95% CI, 1.188‐5.333], p = 0.016), and late complementary feeding (OR 5.438 [95% CI, 2.693‐10.981], p < 0.001) were the predictors for late tolerance development. The estimated optimal cutoff value for introduction of complementary foods for the resolution of allergy was 5.5 months, with 69.4% sensitivity, 74.4% specificity, and an area under the curve of 0.737 (95% CI, 0.626‐0.812) (p < 0.001). Conclusion: This study showed that the early introduction of complementary feeding accelerates tolerance development in FPAIP. A longer duration of an elimination diet has no impact on the resolution of allergy. Physicians should consider conservative avoidance measures and earlier introduction of complementary feeding in FPIAP.

Background Anaphylaxis is a sudden, severe, and potentially life-threatening allergic reaction, affecting a portion of allergic patients. Adrenaline is the first-line medication for anaphylaxis and available in many parts of the world as adrenaline autoinjectors (AAIs). Objective Aim of this study was to determine attitudes and knowledge levels of patients/parents regarding the use of AAIs, frequency, and rate of appropriate AAI use and to give a standardized and better education by improving on mistakes during administration. Method 190 patients aged 1–18 years who were prescribed AAIs for any reason between 2012 and 2017 in Hacettepe University Pediatric Allergy Unit. Demographic data were collected during face-to-face interview or by telephone. Parents completed a mini-survey regarding use, carriage, and storage of AAI. Results Some 190 patients (64.7% male) aged 7.83 (4.99–12.08) years, median (inter-quartile), were included in the study. The indications for AAI prescription were food allergy (78.9%); venom allergy (14.2%); idiopathic anaphylaxis (3.7%); mastocytosis (2.1%); and drug allergy (1.0%). One-fourth of AAI-prescribed patients experienced anaphylaxis requiring the use of AAI within the past five years. However, only 30% of the patients dared to use AAI; only three-quarters of whom had managed to use it correctly. Conclusion After prescription of AAI and initial training, patients and parents’ concerns and fears should be taken into consideration and necessary support should be provided. At every opportunity and each clinical visit, not only should training sessions be repeated but also the patients and parents should be psychologically supported.

Any drug taken at the recommended dosage may cause hypersensitivity reactions (DHR). Rapid drug desensitization (RDD) protocols have been developed in the case of a confirmed or highly suspected HSR to allow safe administration of the medicine when there is no alternative drug or in the presence of a less effective or more toxic alternative. The aim of this study was to evaluate the characteristics of children who underwent desensitization, the safety and efficacy of RDD in children, as well as, the characteristics and management of breakthrough reactions.This retrospective study concerned children who underwent RDD due to physician-diagnosed HSRs during or up to 48 hours after the infusion of various drugs between February 2010-February 2021. Patients with a chronic disease needing chronic drug usage and acute infections seen in patients with chronic diseases were included. The results of RDD were documented.The study included 48 patients [8.1(IQR = 3.32-13.4) years, 60.4% male] with 58 HSRs of which 62.1% were classified as moderate and 5.2% as severe. Most of the patients were being treated for leukemia (41.7%), solid tumors (29.2%), and infections (6.3%). Skin tests were done for 41 out of 58 HSRs in 35 patients, and twenty of them were positive. A total of 269 RDDs were performed for 18 different drugs. Ninety percent of desensitizations were achieved with no reaction, and 3.7% and 5.6% with mild and moderate reactions, respectively. In multivariate analysis, skin test positivity was the only risk factor for breakthrough reactions (OR = 8.5, CI = 1.72-42.15, p = .009).We demonstrated the safety and efficacy of RDD in childhood, thereby offered the first line treatment options to children with chronic diseases with hypersensitivity reactions (HSRs).

BACKGROUND Nutritional status in primary immunodeficiencies (PID) is a major factor influencing immune defense. We aimed to evaluate the nutritional status of patients with PID. METHODS Demographic findings and anthropometric measurements of 104 patients were recorded for this cross-sectional study. RESULTS Combined immunodeficiencies (n = 49), predominantly antibody deficiencies (n = 28) and phagocytic system disorders (n = 17), were the major disease groups. In total, 44 (42.3%) patients had at least one anthropometric measurement below -2 standard deviations. Chronic, acute, and mixed-type malnutrition were detected in 18.3%, 16.3%, and 7.7% of the patients, respectively. No significant difference was detected among groups regarding anthropometric measurements however higher malnutrition rates were observed in 'combined immune deficiency less profound than severe combined immuno deficiency' (52%), chronic granulomatous disease (66.6%), and X-linked agammaglobulinemia (50%) patients. Severe malnutrition was present in 22 (21.2%) of the patients, although it was not significant. It was more common in the phagocytic system disorder group. All patients in the severe combined immunodeficiency group had undergone hematopoietic stem cell transplantation and 50% of them had malnutrition. There was also no significant difference regarding age, sex, anthropometric indexes (Weight for age, lenght/height for age body mass index Z-scores), malnutrition types, and prevalence of malnutrition among three major disease groups. Only the hospitalization history inversely related to body mass index and weight for age Z-scores (P

Leukocyte adhesion deficiency type I is a rare primary immunodeficiency disorder characterized by mutations in the ITGB2 gene encoding CD18. We present clinical and immunological features of 15 patients with leukocyte adhesion deficiency type 1 (LAD-1). Targeted next-generation sequencing was performed with either a primary immunodeficiency gene panel comprising 266 genes or a small LAD-panel consisting of five genes for genetic analysis. To measure the expression level of integrins on the leukocyte surface, flow cytometry analysis was performed. The median age of the patients at diagnosis was 3 (1–48) months. Eleven (73%) of the 15 patients had a LAD-1 diagnosis in their first 6 months and 14 (93%) patients had consanguineous parents. Delayed separation of the umbilical cord was present in 80% (n = 12) of the patients in our cohort, whereas omphalitis was observed in 53% (n = 8) of the patients. Leukocytosis with neutrophil predominance was observed in 73% (n = 11) patients. Nine distinct variants in the ITGB2 gene in 13 of the 15 patients with LAD-1 were characterized, two of which (c.305_306delAA and c.779_786dup) are novel homozygous mutations of ITGB2. Four unrelated patients from Syria had a novel c.305_306delAA mutation that might be a founder effect for patients of Syrian origin. Four (27%) patients underwent hematopoietic stem cell transplantation. Two patients died because of HSCT complications and the other two are alive and well. Early differential diagnosis of the patients is critical in the management of the disease and genetic evaluation provides a basis for family studies and genetic counseling.

The vast majority of primary immunodeficiencies (PIDs) occur due to the defects in cells originating from hematopoietic stem cells, while in some PIDs, there are defects in various genes responsible for non-leucocyte immune response such as seen in epidermodysplasia verruciformis (EV). EV caused by the mutations in TMC6, TMC8, and CIB1 genes is called "typical." "Atypical" EV may develop in patients with primary immunodeficiencies originating from hematopoietic stem cells, which include severe T-cell failure, caused by inactivating biallelic mutations of STK4, RHOH, CORO1A, ITK, TPP2, DCLRE1C, LCK, RASGRP1, or DOCK8 genes. Here, we present a family with TMC8 gene mutation leading to disseminated epidermodysplasia verruciformis including laryngeal papilloma and recurrent cutaneous squamous cell carcinomas. Typical EV with impaired local, keratinocyte-intrinsic immune response should be considered when routine immunological examinations are normal in patients presenting with clinical signs of EV. Although it is not possible to prevent EV lesions, early and appropriate surveillance for malignancy is mandatory.

Atopic dermatitis is the most common skin disease seen during childhood. Other allergic diseases may accompany atopic dermatitis and increased IgE and peripheral blood eosinophilia are common findings. Patients with atopic dermatitis who do not respond to standard treatment measures should be reassessed for differential diagnosis. Early-onset, treatment resistant severe atopic dermatitis with recurrent infection history apart from the infections occurring due to defective skin integrity are the warning signs for an underlying primary immunodeficiency. Clinicians should always remember that atopic dermatitis may be the first finding of an underlying primer immunodeficiency in patients. The sooner the diagnosis is made, the more likely it will be to avoid complications and morbidity.

Bacillus Calmette-Guérin (BCG) vaccine derived from Mycobacterium bovis can cause BCG vaccine associated complications (BCG-VAC) especially in patients with primary immunodeficiencies (PID). No consensus exists for antimycobacterial prophylactic therapy for patients with PID who receive the BCG vaccine.This study aimed to define the risk factors in the development of BCG-VAC and effect of antimycobacterial prophylaxis in PID patients vaccinated with BCG.This is a retrospective cohort study. 104 patients diagnosed with PID who received the BCG vaccination were referred to pediatric pulmonology in a single center were enrolled. The demographic characteristics, type, dosage and duration of antimycobacterial prophylaxis regimen, treatment modalities for BCG-VAC were documented. Regression analysis was performed to evaluate the effect of covariates for predicting BCG-VAC in patients with PIDs.Among 104 patients 21 (21.2%) developed BCG-VAC. The frequency of BCG-VAC was highest in patients with Mendelian susceptibility to mycobacterial disease (46.2%) followed by patients with severe combined immunodeficiency (22.4%) and those with chronic granulomatous disease (9.5%). Prophylactic therapy against mycobacterium was initiated for 72 patients (69.2%). Among patients who received the antimycobacterial prophylaxis, BCG-VAC developed in only four patients (5.6%), whereas 17 patients (53.1%) developed BCG-VAC in the non-prophylaxis group and this difference was statistically significant (p 0.001). Multivariable regression analysis with age at diagnosis, type of PID, receiving antimycobacterial prophylaxis, median T cell number at the time of PID diagnosis and HSCT status showed that not receiving antimycobacterial prophylaxis and lower median T cell number were predictors, with antimycobacterial prophylaxis having the highest odds ratio for BCG-VAC prediction in patients with PIDs (p:0.001, RThe lower frequency of BCG-VAC in our cohort can be explained by two main reasons; relatively late BCG vaccination schedule and receiving antimycobacterial prophylaxis. It is reasonable to begin antimycobacterial prophylaxis in patients with PIDs who are susceptible to BCG-VAC.

V(D)J recombination, during which recognition and repair of broken DNA chains are accomplished by non-homologous end joining pathway, is a critical process in B and T cell development.Null mutations of each enzyme or protein of this pathway result in T- B- NK+ severe combined immunodeficiency whereas hypomorphic mutations result in atypical(leaky)severe combined immunodeficiency forms. We present two siblings with PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) mutation who presented with granulomatous skin lesions and recurrent lung infections. Primary immune deficiencies may initially present with skin findings. Disruption in central and peripheral B-cell tolerance and impaired intrathymic T-cell maturation,a central player in T-cell tolerance, have been identified as the mechanism of autoimmunity and granuloma seen in patients. The variation in clinical phenotypes of patients with PRKDC mutation suggests that additional factors such as modifying genes, epigenetic and environmental factors may affect the severity and clinical phenotype of the disease. Functional studies during the follow-up and evaluation before and after hematopoeitic stem cell transplantation will hopefully increase our knowledge about the autoimmune and inflammatory process of the disease spectrum.

The results and the complications following SARS-CoV2 infection in individuals with primary immunodeficiency(PID) remain unclear. The objective of this study is to report the course, follow-up, outcome of COVID 19 in 26 patients with PIDs from a tertiary PID center in Turkey. Infection mortality rate was found to be %7.69 which is eight times higher than infection mortality rate (%0.97) in general population in Turkey. Although it is clear that mortality in patients with PID is higher than in the normal population, it is difficult to suggest a more risky group among primary immunodeficiencies for COVID-19 with a complicated course according to the data published so far. The groups are quite heterogeneous regarding age, sex and comorbidities, but it is remarkable that patients who underwent HSCT with curative treatment had an uncomplicated course despite comorbidities. Future studies as metaanalysis getting data together may help to get a more reliable conclusion.

Background Serine/threonine kinase-4 (STK4) deficiency is an autosomal recessive combined immunodeficiency. Objective We aimed to define characteristic clinical and laboratory features to aid the differential diagnosis and determine the most suitable therapy. Methods In addition to nine STK4 deficiency patients, we reviewed 15 patients from the medical literature. We compared B lymphocyte subgroups of the cohort with age-matched healthy controls. Results In the cohort, median age at symptom onset and age at diagnosis were 6 years 8 months (range, 6-248 months) and 7 years 5 months (range, 6-260 months), respectively. The main clinical findings were infections (in all nine patients [9 of 9]), autoimmune or inflammatory diseases (7 of 9), and atopy (4 of 9). CD4 lymphopenia (9 out 9), lymphopenia (7 out 9), intermittent eosinophilia (4 out 9), transient neutropenia (3 out 9), low IgM (4 out 9), and high IgE (4 out 9) were common. Decreased recent thymic emigrants, naive and central memory T cells, but increased effector memory T cells were present. The increase in plasmablasts (P = .003) and decrease in switched memory B cells (P = .022) were significant. When 24 patients are analyzed, cutaneous viral infections (n = 20), recurrent pneumonia (n = 18), Epstein Barr virus–associated lymphoproliferation (n = 11), atopic dermatitis (n = 10), autoimmune cytopenia (n = 7), and lymphoma (n = 6) were frequent. Lymphopenia, CD4 lymphopenia, high IgG, IgA, and IgE were common laboratory characteristics. Conclusions The differential diagnosis with autosomal recessive hyper-IgE syndrome is crucial. Because, atopy and CD4 lymphopenia are common in both diseases. Immunoglobulins, antibacterial, and antiviral prophylaxis are the mainstays of treatment. Clinicians may use immunomodulatory therapies during inflammatory or autoimmune complications. However, more data are needed to recommend hematopoietic stem cell transplantation as a safe therapy.

Background Pistachio and cashew nut, which belong to the same botanical family, are tree nuts that induce serious allergic reactions. Objective We aimed to determine the predictive factors for pistachio and cashew nut reactivity during oral food challenge (OFC). Methods A total of 112 pistachio and/or cashew nut sensitized children, aged 58.45 (IQR:40.38-88.32) months, were included. Cutoff values and probability curves for skin prick test (SPT), sIgE, sIgE/Total IgE that predict reactivity were determined for pistachio and cashew nut. Additionally, a diagram was created that can be useful while making a decision for OFC based on SPT and sIgE values. Results A total of 73 patients underwent OFC with pistachio and/or cashew nut. Twelve children with current anaphylaxis history were not challenged and accepted as allergic. SPT was the only predictive factor for positive pistachio/ cashew nut OFC. According to area under curve (AUC) analysis, SPT was more predictive than sIgE and sIgE/Total IgE both for pistachio and cashew nut. Optimal cutoff values according to "Youden index" for pistachio SPT, sIgE, and sIgE/ Total IgE were 7.25 mm, 4.14 kUA/L, and 1.32%, respectively. And those values for cashew nut SPT, sIgE, and sIgE/Total IgE were 6.25 mm, 1.125 kUA/L, and 3.30%, respectively. The diagram showed that SPT predicted the reactivity together with sIgE better than only the SPT values. Conclusion SPT was the best predictor for reactivity both for pistachio and cashew nut. Combined use of SPT and sIgE may improve the prediction of reactivity at pistachio and cashew nut OFCs in children.

BACKGROUND Several markers that influence the clinical course of atopic dermatitis (AD) have been investigated so far. Thymus and activation regulated chemokine (TARC) - a Th2-related cytokine - increase in various atopic diseases. It has been shown that vitamin D affects Treg cells and immune responses. Zinc as an essential trace element for cell-cell interactions, cellular differentiation, and proliferation. However, the effect of these markers on infantile AD and disease severity are mostly unknown. OBJECTIVE The aim of this study was to investigate the relationship between TARC, vitamin D, zinc levels, and the disease severity in infants with AD. METHOD AD patients (n = 160) with age and sex that matched healthy controls (n = 79) were included in the study. The diagnosis of AD was made based on the Hanifin-Rajka criteria. The objective SCORAD index was used for the assessment of disease severity. RESULTS A total of 160 patients (male 71.9%) with AD were included in the study. The median age of onset of symptoms was 2 (1.0-3.5) months. The lesions initially started on face 76.9%, neck 6.9%, extremities 7.5%, and body 8.8%. Nearly 40% of the patients were found to be atopic. Food allergy was found in 39.4%. The median of objective SCORAD index was 27.5 (17.5-40) in the study group. The TARC levels of AD patients were higher than control group [1803 pg/ml (1006- 3123) vs 709 pg/ml (504-1147), p < 0.001] There was a significant correlation between objective SCORAD scores and TARC values in subjects with AD (r = 0.363, p < 0.001). As the severity of AD increased, vitamin D levels decreased (p for trend 0.015) and TARC values increased (p for trend < 0.001). Serum zinc levels did not change with the severity of the disease. The presence of atopy did not have an influence on serum TARC, zinc, and vitamin D levels. CONCLUSION In infants with AD, disease severity is positively related with TARC levels; and inversely proportional to vitamin D levels. TARC levels differ between patients and healthy controls. The presence of atopy has not been shown to affect these markers. © 2021 Codon Publications. Published by Codon Publications.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. Certain gene loci are pointed out in several studies in CVID patients. Until now, monogenic defects have been identified in only 2-10% of CVID patients; therefore, association of the disease with HLA alleles may be important for elucidating immunological and genetic mechanisms behind CVID. The aim of this study is to investigate the relationship between CVID and HLA alleles.HLA class I/II alleles were analyzed in 65 patients with CVID and alleles that may be related to disease susceptibility were determined by comparing with 300 healthy controls. We also evaluated HLA allele frequencies in CVID patients with gastrointestial system (GIS) involvement and autoimmune manifestations.When compared with controls, frequencies of B*27, B*35, C*04, and DRB1*04 alleles were significantly different in patients with CVID (In comparison with literature, distinctive HLA alleles found in our study may originate from the diversity in gene pool between the populations. These data may provide clues for disease susceptibility.

Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT). Measurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. One of the patients with late-onset ADA deficiency was diagnosed by the help of primary immunodeficiency panel screening. Ten out of 13 patients were diagnosed as SCID, while 3 out of 13 were diagnosed as delayed-/late-onset ADA deficiency. Late-onset ADA deficiency patients had clinical and laboratory findings of combined immunodeficiency (CID). Eight patients with ADA-SCID were found to have higher levels of ADA metabolite (dAXP%) (62.1% (34.6-71.9)) than 3 patients with delayed-/late-onset ADA deficiency (6.9% (2.1-8.9). All but one patient with SCID had T-B-NK- phenotype, one had T-B-NK+ phenotype. Genetic defect was documented in 11 patients. Four out of 11 patients had compound heterozygous defects. Three out of 4 patients with compound heterozygous defects had delayed-onset/late-onset ADA deficiency. Seven out of 11 patients with SCID had homozygous defects. Five out of 7 had the same homozygous indel frameshift mutation (c.955-959delGAAGA) showing a founder effect. There were two novel splice site defects: one (IVS10+2T > C) was heterozygous in a patient with late-onset ADA deficiency, and the other was homozygous (IVS2delT+2) in a SCID patient. Other defects were missense defects. Nine out of 13 patients were put on pegylated ADA ERT. Four out of six patients were transplanted without using a conditioning regimen. HSCGT was performed to one of the patients. The genetic diagnosis of SCID is utmost important. There is a chance to give ERT before the definitive therapy if the patient with SCID/CID has ADA deficiency. Although ERT was insufficient to restore a normal immune function in ADA-SCID patients, it was useful to improve and stabilize the clinical status before curative therapy (aHSCT/HSCGT). Enzyme replacement therapy was successful in patients with late-/delayed-onset ADA deficiency who presented with the features of combined immunodeficiency. Gastrointestinal polyposis in a patient with late-onset ADA deficiency may be an association or a coincidental finding. Intermittent neurodevelopmental evaluation especially for hearing impairment should be performed in most of the ADA-deficient patients. This may alleviate the speech delay and cognitive abnormalities which may be observed in the follow-up.

Background Venom immunotherapy (VIT) is safe in children, although adverse effects can occur. Objective To document adverse effects and to determine re-sting reactions and the efficacy of VIT in childhood. Methods We retrospectively analyzed data from children who had taken VIT from 2002 through 2015. These patients were queried by telephone to determine reactions after re-stings during or after VIT. Results In total 107 children with a systemic reaction after Hymenoptera sting and with proved immunoglobulin E-mediated sensitization were enrolled. Participants had a median age of 10.0 years (7.2–12.4 years) at the beginning of immunotherapy. Fifty-two participants had allergic reactions during VIT; 40 of these reactions were local (37.4%), 5 were large local (4.7%), and 7 were systemic (6.5%). Of the 52 patients with adverse reactions, most reactions were local (n = 40, 89%) and were observed mainly in dose-increase periods (n = 25, 60%; P Vespula treatment ( P = .047), systemic reactions were common with Apis treatment ( P = .031). Sixty-eight patients (63.5%) were queried for re-sting, 33 (48.5%) had a re-sting and 24 (72.7%) of these 33 patients developed allergic reactions. The reactions were local (n = 19), large local (n = 1), and systemic (n = 4). Risk analysis for local and systemic reactions during VIT showed pre-existing asthma as an independent risk factor (odds ratio 4.1, 95% confidence interval 1.3–12.7, P = .016). Conclusion In children, VIT appears to be safe and protective against severe reactions after re-sting. However, pre-existing asthma was identified as a risk factor for systemic and large local reactions during VIT in children.

BACKGROUND Although data on anaphylaxis in the general population exist for different allergens, there is still lack of detailed etiologic data on drug-induced anaphylaxis (DIA), particularly in children. OBJECTIVE To define the etiology of DIA, to determine the accuracy of drug-related anaphylaxis histories, along with the severity and culprit drug associations among individuals

• In the patients with atypical presentations of vasculitis, suspicion of monogenic disorders may avoid delays in diagnosis and treatment.

Introduction Autosomal recessively inherited lipopolysaccharide-responsive beige-like anchor (LRBA) protein deficiency was shown to be responsible for different types of inborn errors of immunity, such as common variable immunodeficiency (CVID) and autoimmune lymphoproliferative syndrome (ALPS). The aim of this study was to compare patients with LRBA-related ALPS and LRBA-related CVID, to describe their clinical and laboratory phenotypes, and to prepare an algorithm for their diagnosis and management. Methods Fifteen LRBA-deficient patients were identified among 31 CVID and 14 possible ALPS patients with Western blotting (WB), primary immunodeficiency disease (PIDD) gene, next-generation panel screening (NGS), and whole exome sequencing (WES). Results The median age on admission and age of diagnosis were 7 years (0.3-16.5) and 11 years (5-44), respectively. Splenomegaly was seen in 93.3% (14/15) of the patients on admission. Splenectomy was performed to 1/5. Recurrent upper respiratory tract infections (93.3% (14/15)), autoimmune cytopenia (80% (12/15)), chronic diarrhea (53.3% (8/15)), lower respiratory tract infections (53.3% (8/15)), lymphoma (26.6% (4/15)), Evans syndrome (26.6% (4/15)), and autoimmune thyroiditis (20% (3/15)) were common clinical findings and diseases. Lymphopenia (5/15), intermittant neutropenia (4/15), eosinophilia (4/15), and progressive hypogammaglobulinemia are recorded in given number of patients. Double negative T cells (TCR alpha beta(+)CD4(-)CD8(-)) were increased in 80% (8/10) of the patients. B cell percentage/numbers were low in 60% (9/15) of the patients on admission. Decreased switched memory B cells, decreased naive and recent thymic emigrant (RTE) Thelper (Th) cells, markedly increased effector memory/effector memory RA(+) (TEMRA) Th were documented. Large PD1(+) population, increased memory, and enlarged follicular helper T cell population in the CD4(+) T cell compartment was seen in one of the patients. Most of the deleterious missense mutations were located in the DUF1088 and BEACH domains. Interestingly, one of the two siblings with the same homozygous LRBA defect did not have any clinical symptom. Hematopoietic stem cell transplantation (HSCT) was performed to 7/15 (46.6%) of the patients. Transplanted patients are alive and well after a median of 2 years (1-3). In total, one patient died from sepsis during adulthood before HSCT. Conclusion Patients with LRBA deficiency may initially be diagnosed as CVID or ALPS in the clinical practice. Progressive decrease in B cells as well as IgG in ALPS-like patients and addition of IBD symptoms in the follow-up should raise the suspicion for LRBA deficiency. Decreased switched memory B cells, decreased naive and recent thymic emigrant (RTE) Th cells, and markedly increased effector memory/effector memory RA(+) Th cells (TEMRA Th) cells are important for the diagnosis of the patients in addition to clinical features. Analysis of protein by either WB or flow cytometry is required when the clinicians come across especially with missense LRBA variants of uncertain significance. High rate of malignancy shows the regulatory T cell's important role of immune surveillance. HSCT is curative and succesful in patients with HLA-matched family donor.

Background/aim: The aim of this study was to compare the effect of salbutamol delivered to children by jet nebulizer (JN) and mesh nebulizer (MN). Materials and methods: Children admitted with acute asthma were treated with 3 doses of nebulized salbutamol, 1 given by MN. The patients' vital signs, lung function measurements, modified pulmonary index score (MPIS), and whole body plethysmography (WBP) measurements were evaluated before and 20 min after each dose of salbutamol.Results: Thirty-onechildren [9.5 (6.4-17.2) years, 67.7% male, 32.3% female] with mild (67.7%) and moderate (32.3%) asthma attacks were included in the study. The improvements with MN were comparable with JN in terms of changes in pretreatment and posttreatment forced expiratory volume in the first second (FEV1) (2.57 ± 4.57, 3.65 ± 5.44; P = 0.44), forced vital capacity (FVC) (2.52 ± 5.29, 4.17 ± 7.54; P = 0.28), heart rate (7.33 ± 10.21, 4.14 ± 9.32; P = 0.24), peripheral capillary oxygen saturation (SpO2) (0.38 ± 0.23, 0.43 ± 0.15; P = 0.83), and modified pulmonary index score (MPIS) (-6.30 ± 22.70, -8.77 ± 25.46; P = 0.70). The pre- and posttreatment values of total lung capacity (TLC), residual volume (RV), specific conductance (sGaw), and RV/TLC were similar for the JN and MN groups. Adverse effects were not different: however, complaints of palpitation were significantly higher in the posttreatment MN group than the pretreatment MN group (32.3% vs 9.7%, respectively, P = 0.016).Conclusions: These findings support the previous evidence found in studies of adults that MN is as effective as and as safe as JN in the treatment of acute asthma in children.

Cytokine storm syndromes (CSS) are a challenge for physicians, both due to their aggressive nature and the need for tailored treatment for each patient. While hematopoietic stem cell transplantation (HSCT) has changed the fate of primary hemophagocytic lymphohistiocytosis (HLH), and biologics of macrophage activation syndrome (MAS)/secondary HLH, there is still a need for adjunctive treatment to better manage these patients. The principles of treatment are summarized in Table 1. This chapter discusses the available alternative treatments (biologics discussed in elsewhere). Unfortunately, except for corticosteroids, there is not a lot of solid evidence for the effectiveness of most of these agents. Biologics have become an essential part of the treatment in MAS. However for all these treatment modalities and corticosteroids, there is a lack of controlled studies to guide optimal dosage and duration of therapy.

X-linked agammaglobulinemia is a primary immunodeficiency disorder resulting from BTK gene mutations. There are many studies in the literature suggesting contradictory ideas about phenotype-genotype correlation. The aim of this study was to identify the mutations and clinical findings of patients with XLA in Turkey, to determine long-term complications related to the disease and to analyse the phenotype-genotype correlation. Thirty-two patients with XLA diagnosed between 1985 and 2016 in Pediatric Immunology Department of Hacettepe University Ihsan Dogramaci Children's Hospital were investigated. A clinical survey including clinical features of the patients was completed, and thirty-two patients from 26 different families were included in the study. Getting early diagnosis and regular assessment with imaging techniques seem to be the most important issues for improving the health status of the patients with XLA. Early molecular analysis gives chance for definitive diagnosis and genetic counselling, but not for predicting the clinical severity and prognosis.

Interstitial lung disease (ILD) is a rare and heterogeneous group of disorder affecting the lung parenchyma and has a detrimental effect on gas exchange. Chronic granulomatous disease (CGD), when it affects primarily lungs, may cause ILD. We report a 16-year-old patient with CGD caused by homozygous deletion of NCF1 who atypically presented with ILD. The patient had many pigeons and was a pigeon breeder. Exacerbated clinical symptoms were linked to hypersensitivity pneumonitis (HP), and the patient was suggested to keep away from pigeons. In addition to allergen avoidance and prophylactic antibacterial therapy, treatment with corticosteroids and hydroxychloroquine was started for mainly obstructive and persistant symptoms of ILD. CGD is known to cause a hyperinflammatory state and the patients present with excessive granuloma formation and HP. Control of inflammation either by avoidance of allergen exposure and by anti-inflammatory drugs is necessary for the relief of symptoms.

Esenboğa S, Şekerel BE. Exercise-induced anaphylaxis: a case report and review of the literature. Turk J Pediatr 2019; 61: 440-443. Exercise-induced anaphylaxis (EIAn) is a rare, unpredictable, and potentially fatal cause of anaphylaxis which occurs with physical exhaustion. To the best of our knowledge, here we report the first case of EIAn from Turkey with no prior history of allergy. A detailed patient history is the most crucial point in the diagnosis of EIAn. The triggering and co-factors should be questioned in detail to determine treatment recommendations.

Combined immunodeficiencies (CIDs) comprise a heterogeneous group of monogenic disorders manifesting with lymphocyte defects, recurrent infections and dysregulated immune response. Recently, we and others have described clinical and molecular features of the combined immunodeficiency syndromes

Hypoglycemia as an umbilical artery catheter (UAC) complication is rare. We present a neonate with hyperinsulinemic hypoglycemia due to a high-positioned UAC used inadvertently for parenteral nutrition. The aim of this report is to increase physicians ’ awareness of the possibility of this rare complication.